The following description of the background of the invention is provided simply as an aid in understanding the invention and is not admitted to describe or constitute prior art to the invention.
As discussed in Fredline et al. Clin. Chem. 45: 659-664 (1999), renin is a proteolytic enzyme secreted into blood by the juxtaglomerular cells of the kidney. Renin acts on angiotensinogen, to produce a decapeptide referred to as angiotensin 1 (Ang1). Ang1 is further cleaved by angiotensin-converting enzyme to form an octapeptide, referred to as angiotensin 2 (Ang2). Ang2 stimulates cell growth, renal tubule transport of sodium, and aldosterone release. Ang2 is one of the most potent vasopressors in humans and plays an important role in blood pressure regulation. Direct measurement of Ang2 is difficult because of its very low circulating concentrations and extremely short half-life; Ang1, which is more stable than Ang2, provides a better analyte to measure the state of the renin-angiotensin system. Determination of a “plasma renin activity” (PRA) from the rate of generation of Ang1 is used clinically for the diagnosis and management of hypertension.
The classical method for the determining PRA is radioimmunoassay (RIA), see Sealey, Clin. Chem. 37: 1811-1819 (1991); Sommer, et al. , Horm Res. 37:171-175(1992); Shionoiri et al., A J Med Sci., 300(3):138-43(1990).
For example, Fredline et al. describes measurement of plasma renin activity with the use of HPLC-electrospray-tandem mass spectrometry. In doing this measurement, Fredline et al. incubates plasma samples in the presence of a water-sensitive enzyme inhibitor (i.e., phenylmethylsulphonyl fluoride (PMSF)) and measures the amount of angiotensin 1 generated during incubation by observing the collision induced dissociation of precursor ions with a (m/z) of 649.